The present invention relates to an apparatus for separating ions, an ion mobility separator or spectrometer, a mass spectrometer, a method of separating ions and a method of mass spectrometry.
Ion mobility separation or ion mobility spectrometry is a method which may be used to separate ionic species at atmospheric pressures. The method may also be used at sub-atmospheric pressures provided that the mean free path of an ion in an ion mobility separator or ion mobility spectrometer is sufficiently small such that gas flow is viscous and not molecular.
Ion mobility spectrometers are used as analytical detectors and have a number of different applications. Ion mobility spectrometers are sometimes used, for example, for explosive and chemical warfare agent detection. Airports, for example, may use ion mobility spectrometers for detecting explosives and some government agencies carry ion mobility spectrometers on raids for on-site identification of drugs of abuse. On-site monitoring of pesticides, chemical warfare agents and industrial chemicals is another application for ion mobility spectrometers.
Ion mobility separators may be used to rapidly separate complex biological mixtures prior to analysis by mass spectrometry.
A known ion mobility spectrometer comprises an ion source, an ion gate, a drift tube and an ion detector. A sample to be analysed is ionised in the ion source and is then passed or transmitted to or passed to the ion gate. The ion gate is then pulsed ON and OFF to allow short pulses of ions to be emitted into the drift tube. The drift tube comprises a plurality of electrodes arranged along the length of the drift tube. A relatively high strength DC electric field is maintained along the length of the drift tube in order to propel or urge ions along and through the drift tube against a counterflow of gas. A gas inlet is provided adjacent to the drift tube exit region and a gas outlet is provided adjacent to the drift tube entrance region. Gas is arranged to flow through the drift tube in the opposite direction to the direct of travel of the ions. The drift gas flow rate may be varied in order to change the ionization spectra to alter selectivity.
Packets of ions are propelled from the ionisation region through the drift tube of the ion mobility spectrometer to the ion detector which is arranged at the exit region of the drift tube. Ions become separated within the drift region according to their ion mobility as they are urged against the counter flow of gas. The electric field is used to drag, propel or urge the ions through or against the drift gas which is sufficiently dense that the ions rapidly reach a terminal velocity. The terminal velocity is to a first approximation proportional to the strength of the applied electric field. The terminal velocity is also proportional to the mobility of the ion. Accordingly, ions can be separated from one another according to their ion mobility. The ion mobility of an ion is generally closely related to its cross sectional area and its charge.
Ionisation sources for ion mobility spectrometers of samples in the gaseous phase include radioactive nickel, Atmospheric Pressure Chemical Ionisation ion sources and photoionisation ion sources. More recently ion mobility spectrometry of polar samples in liquid solution has become possible using Electrospray Ionization (“ESI”).
Ion mobility spectrometers provide simple, inexpensive, high throughput screening under ambient conditions.
More recently a variation of a conventional ion mobility spectrometer has been developed known as a Field Asymmetric Ion Mobility Spectrometry (“FAIMS”) device. FAIMS devices differ from conventional ion mobility spectrometers in that ions of different species are separated within a FAIMS device according to their rate of change of ion mobility with electric field strength rather than their ion mobility per se. FAIMS devices are capable of separating gas-phase ions at atmospheric pressures and ambient temperatures but can also be operated over a wide range of pressures and temperatures.
Field Asymmetric Ion Mobility Spectrometry devices typically utilise relatively strong or high periodic electric fields which may, for example, have a field strength of approximately 10,000 V/cm. The periodic electrical fields or waveforms which are used to separate ions are asymmetric i.e. there is a difference between the magnitude of the peak positive voltage and the magnitude of the peak negative voltage of the applied electric field or waveform. Either the peak positive or the peak negative voltage may be the higher.
Field Asymmetric Ion Mobility Spectrometry devices utilise an electric field to drag or propel ions through a gas that is sufficiently dense such that the ions rapidly reach a terminal velocity. The terminal velocity is approximately proportional to the strength of the electric field. However, this proportionality changes at high electric field strengths and is also compound-dependent. Accordingly, the compound specific variation in ion mobility with electric field strength can be used to separate ions from each other.
The rate of change of ion mobility with change in electric field strength is not currently believed to be directly related to the mobility of the ion. The change of mobility with electric field strength is not currently very well understood and is generally considered to be largely unpredictable. It is possible that the rate of change of ion mobility is dependent upon the susceptibility of an ion to distort in the presence of a strong electric field.
A known FAIMS device comprises two metal plates or electrodes. An asymmetric voltage or potential is applied to the metal plates or electrodes such that a time varying asymmetric electric field is generated between the metal plates or electrodes. If a mixture of ions of different sizes and types is introduced between the two metal plates or electrodes, then the application of an appropriate asymmetric voltage waveform to the plates or electrodes will create a condition wherein some types of ion will tend to drift towards and hit one of the metal plates or electrodes whilst other types of ion will tend to remain located between the plates or electrodes. The asymmetric voltage waveform may, for example, comprise a square wave wherein a relatively high positive voltage is applied for a relatively short period of time and a relatively low negative voltage is applied for a relatively long period of time (or vice versa).
If the electric field which is created by the application of the asymmetric voltage or waveform is relatively weak (e.g. if the electric field strength is less than 200 V/cm) then ions will tend to move back and forth, or otherwise oscillate between the plates or electrodes, during the application of the asymmetric voltage waveform. The ions will not tend to move towards either plate or electrode. If, however, the electric field which is created during a high-voltage part of the asymmetric voltage or waveform is relatively strong or high (e.g. if the electric field strength exceeds, for example, about 5000 V/cm) then the ions will then tend to drift towards one or other of the plates or electrodes.
An ion will drift towards a plate or electrode due to the fact that the mobility of the ion during the application of a relatively high strength electric field is different to the mobility of the ion during the application of a relatively low strength electric field. Since the mobility of the ion defines how fast the ion moves in an electric field, the ion will move proportionately farther in a relatively high strength electric field than the ion will move in a relatively low strength electric field (or vice versa).
The asymmetric voltage waveform which is typically applied tends to have a relatively high frequency e.g. ≧200 kHz. The small extra distance travelled during each high-voltage period of a voltage waveform results in a net drift of the ion towards one of the plates.
Some ions exhibit a mobility which increases with electric field strength whilst other ions exhibit a mobility which decreases with electric field strength. As a result different ions can travel in opposite directions between the plates or electrodes during the application of an asymmetric voltage waveform. Certain ions, for example, such as the chloride ion in nitrogen or oxygen gas experience very large changes in mobility as a function of electric field strength. During the application of an asymmetric waveform, chloride ions will therefore drift very rapidly towards a plate or electrode. On the other hand, some ions, such as the tetrapropylammonium ion exhibit only a very small relative change in ion mobility with electric field strength and hence will tend to drift only very slowly towards one of the plates or electrodes.
The relative or net drift of an ion towards one of the metal plates or electrodes can be stopped or otherwise counter-balanced by applying a small compensation DC voltage to one of the plates or electrodes. If the compensation voltage is arranged to have a specific magnitude and polarity then specific species of ions can be arranged to experience an electric force which counteracts the force on the ion towards one of the plates or electrodes. As a result the overall net drift of the ion towards one of the plates or electrodes will be zero. The voltage that is applied in order to reverse or compensate for the ion drift is commonly known as the compensation voltage (“CV”).
The compensation voltage necessary to stop or counteract the drift of a chloride ion will be relatively high since the mobility of chloride ions increases significantly at high electric field strengths. On the other hand, the compensation voltage necessary to stop or counteract the drift of tetrapropylammonium ions will be relatively small. It is therefore apparent that by appropriate selection and setting of the compensation voltage certain ions can be selected to experience zero net force (and hence will be transmitted through the FAIMS device without impinging upon the plates or electrodes) whilst the majority of other ions will experience a non-zero net force and hence will tend to collide with one of the plates or electrodes and hence become lost to the system.
If a mixture of ions is placed between the two plates or electrodes of a FAIMS device and a high voltage asymmetric waveform is applied to the plate or electrodes, then different types of ions will begin to migrate towards the plates or electrodes at rates which are characteristic of those ions. If a specific DC compensation voltage is also applied to the plates or electrodes then most ions will hit the plates whilst some ions for which the compensation voltage is exactly the right voltage to provide an electric force which counter balances or compensates for the drift caused by the application of the asymmetric waveform will not drift towards the plates or electrodes. These ions will instead emerge from the FAIMS device. A complex mixture of ions can therefore become separated by using a FAIMS device. The types of ion that are in a balanced or equilibrium condition between the plates or electrodes of a FAIMS device can be selected or varied by adjusting the DC compensation voltage applied to the plates or electrodes.
A mixture of ions carried by a gas flow in a FAIMS device can be resolved into several peaks by scanning (i.e. varying) the DC compensation voltage and simultaneously detecting the ions successfully transported through the gap between the plates or electrodes. Different types of ion will travel or pass between the plates or electrodes at different specific characteristic DC compensation voltages. The spectrum of peaks observed in this manner is referred to as a compensation voltage spectrum.
An alternative known Field Asymmetric Ion Mobility Spectrometry device comprises two concentric cylindrical electrodes instead of two planar electrodes. An asymmetric voltage waveform and a DC compensation voltage are applied to the inner and outer cylindrical electrodes. If the polarity of the asymmetric waveform is such that a specific ion species is caused to drift towards the inner cylindrical electrode in the absence of a compensation voltage, then the application of an appropriate DC compensation voltage can be arranged so as to introduce an additional force which repels the ion away from the inner cylindrical electrode. The drift towards an electrode is therefore counterbalanced by a compensation electric field which will balance at a certain radial distance. If the ion is nearer to the inner cylindrical electrode then it will migrate away from the inner cylindrical electrode to a radial position wherein the compensation field is balanced. Similarly, if the ion is nearer to the outer cylindrical electrode then it will migrate away from the outer cylindrical electrode towards a radial position wherein the compensation field is balanced. As a result different species of ions become focused at different fixed radial positions between the two concentric cylindrical electrodes. The ions are distributed around an ideal or theoretical radial position due to diffusion, space charge ion-ion repulsion and gas turbulence/movement effects.
A similar focusing effect can be obtained with concentric spheres. Another known Field Asymmetric Ion Mobility Spectrometry device comprises two concentric cylindrical electrodes which terminate as two concentric hemispherical sections at one end. This arrangement can be used to further concentrate specific ions at one end of the FAIMS device.
Known ion mobility spectrometers or separators suffer from a relatively poor resolution in that known ion mobility spectrometers or separators can only separate ions of different mobilities with a relatively low or poor resolution of e.g. typically 1 part in 20 and at best 1 part in 50. Factors that determine the resolution of known ion mobility spectrometers or separators include the initial ion pulse width, the broadening due to Coulomb repulsion between ions in both the ionization and drift regions, the spatial broadening due to diffusion of ion packet and the ion-molecule reactions in the drift region. The Coulomb contribution to the resolution depends on the total number of ions initially generated.
For some applications the low resolution inherent with known ion mobility spectrometers or separators is too low and can lead to false positives. For example, if an ion mobility spectrometer is used to detect chemicals used in explosives, or bio-chemicals used as nerve agents in weapons of mass destruction, then another unrelated chemical that may be present may be detected and mistaken for a targeted chemical reagent.
Similarly, known Field Asymmetric Ion Mobility Spectrometry devices also suffer from relatively poor resolution i.e. they are capable of separating ions of different mobility susceptibility to field strength to only typically 1 part in 20 or at best 1 part in 50. For some applications this relatively low resolution can also lead to false positives.